Mitochondrial DNA changes in pedunculopontine cholinergic neurons in Parkinson disease

• Published in: Annals of neurology 2017-12, Vol.82 (6), p.1016-1021
• Main Authors: Bury, Alexander G., Pyle, Angela, Elson, Joanna L., Greaves, Laura, Morris, Christopher M., Hudson, Gavin, Pienaar, Ilse S.
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Brain stem; Cholinergic Neurons - metabolism; Cholinergic Neurons - pathology; Copy number; Deoxyribonucleic acid; DNA; DNA, Mitochondrial - genetics; DNA, Mitochondrial - metabolism; Dopamine receptors; Female; Humans; Male; Mitochondrial DNA; Movement disorders; Neurodegenerative diseases; Neurons; Oxidative phosphorylation; Parkinson Disease - genetics; Parkinson Disease - metabolism; Parkinson Disease - pathology; Parkinson's disease; Patients; Pedunculopontine tegmental nucleus; Pedunculopontine Tegmental Nucleus - metabolism; Pedunculopontine Tegmental Nucleus - pathology; Phosphorylation; Substantia nigra
• ISSN: 0364-5134; 1531-8249
• DOI: 10.1002/ana.25099

In Parkinson disease (PD), mitochondrial dysfunction associates with nigral dopaminergic neuronal loss. Cholinergic neuronal loss co‐occurs, particularly within a brainstem structure, the pedunculopontine nucleus (PPN). We isolated single cholinergic neurons from postmortem PPNs of aged controls and PD patients. Mitochondrial DNA (mtDNA) copy number and mtDNA deletions were increased significantly in PD patients compared to controls. Furthermore, compared to controls the PD patients had significantly more PPN cholinergic neurons containing mtDNA deletion levels exceeding 60%, a level associated with deleterious effects on oxidative phosphorylation. The current results differ from studies reporting mtDNA depletion in nigral dopaminergic neurons of PD patients. Ann Neurol 2017;82:1016–1021